P1226: A RETROSPECTIVE REVIEW OF SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS FROM A TEACHING HOSPITAL IN SINGAPORE.
Authors: A. C. Y. Tso, S. Z. Fong, L. K. Lee, V. S. Sampath, B. E. Fan, S. S. W. Chan, K. H. Ong
Journal: HemaSphere (2022)

Background: Secondary Hemophagocytic Lymphohistiocytosis (HLH) is an aggressive life-threatening syndrome leading to uncontrolled immune hyperactivation and end organ failure. Real world data on the outcome of secondary HLH amongst Asians are limited to small case series. Aims: The purpose of this paper is to describe the patient profiles, aetiologies and survival outcomes of adult patients with secondary HLH in a tertiary hospital in Singapore. Methods: This is a retrospective medical records review of adult patients with secondary HLH between March 2015 and June 2020. Ethics approval was obtained (DSRB 2020/00833). Survival probabilities over time were estimated using the Kaplan–Meier method and their distributions between malignancy and non-malignancy-associated HLH were compared using log rank test. Hazard ratios (HR), along with 95% confidence intervals (CI), were estimated using Cox proportional hazard models. Results: 36 patients (18 females, 18 males) aged 23 to 80 were followed up for a median 14 months. 16 had underlying aggressive lymphomas (B cell (N=5), T cell (N=5), NK/T cell (N=5), unknown subtype (N=1)). 15 had underlying viral infections (11 Dengue, 2 EBV, 1 parvovirus, 1 unknown). No cause was found in 5 patients. Of the 30 patients who had tissue biopsies performed, 28 (93.3%) demonstrated hemophagocytosis. The mean HSCORE was 234.3 indicating >96% probability for HLH. Treatment: 65% patients without an underlying malignancy required HLH-directed therapy and blood product transfusion. This is in contrast with 100% patients with an underlying malignancy. 13 of 16 patients with aggressive lymphomas were also treated with systemic chemotherapy. 2 patients with aggressive T cell lymphoma underwent stem cell transplantation. Overall survival: Malignancy-associated HLH patients had poorer survival compared to non-malignancy-associated HLH (median OS 1.5 months vs not reached, p value 0.01). The 1-year survival rates of patients with malignancy-associated HLH, HLH with unknown aetiologies and infection-associated HLH were 0.312 (95% CI: 0.151 – 0.646), 0.400 (95% CI: 0.137 – 1.000) and 0.867 (95% CI: 0.711 – 1.000), respectively. Regression analysis revealed that malignancy significantly increased the risk of death when compared to infection-associated HLH (HR 7.74, 95% CI: 1.72 – 34.8, p value 0.007). These remained significant after adjusting for differential distribution in age, gender and ethnicity. Within different subtypes of malignancy, we found that NK/T cell lymphoma had the worst survival outcome, followed by T cell and B cell lymphoma (median OS time 0.6, 2 and 19 months, respectively). The adjusted hazard ratios suggested the risk of death among patients with NK/T cell lymphoma was as big as seven times compared to B cell lymphoma, but it didn’t reach to statistical significance (HR 7.33, 95% CI: 0.96 – 55.98, p value 0.055). Image:Summary/Conclusion: Our case series highlight the stark contrast in the overall survival of secondary HLH patients with and without an underlying malignancy. The outcome of malignancy-associated HLH in our study was similar to MD Anderson Cancer Center’s experience (25% and 20% overall survival respectively; with a median survival of 1.5 months in both). Prompt recognition amongst physicians likely to encounter HLH, early referral to hematologists, prompt initiation of HLH-directed and supportive therapies and tackling underlying triggers, are key to improving the outcome of secondary HLH.